An Unusual Case of Mixed-Dust Exposure

An Unusual Case of Mixed-Dust Exposure Involving a "Noncommercial" Asbestos.

by Ronald F. Dodson , Jeffrey L. Levin

Our health center evaluated an individual for suspected pneumoconiosis, which
had resulted from exposures in a foundry/metal reclamation facility. Appropriate
consent forms were obtained for the procedures. Historically, individuals who
work in foundries have been exposed to various types of dusts. The clinical
findings in this case were consistent with silicosis with a suspicion of
asbestos-induced changes as well. A sample from this individual, analyzed by
electron microscopy, showed both classical and atypical ferruginous bodies. The
uncoated fiber burden in this individual indicated an appreciable number of
anthophyllite asbestos fibers. This finding, coupled with analysis of cores from
ferruginous bodies and the presence of ferruginous bodies in areas of
interstitial fibrosis, pathologically supported the diagnosis of
asbestos-related disease. The unique factor associated with this case is that
unlike in some settings in Finland where anthophyllite was mined and used
commercially, this mineral fiber is not commonly found in commercially used
asbestos products in the United States. Although the actual source of the
asbestos exposure in this case is still being sought, it should be recognized
that anthophyllite is a contaminant of many other minerals used in workplace
environments, including foundries. The fiber burden indicates a unique type of
exposure, differing from that usually construed as typical in occupational
settings in the United States. Key words: amphibole, anthophyllite, asbestos,
microscopy, pneumoconiosis. Environ Health Perspect 109:199-203 (2001). [Online
29 January 2001]
http://ehpnet1.niehs.nih.gov/docs/2001/109p199-203dodson/abstract.html

Case Report

This individual was first seen in early 1996 for respiratory symptoms of cough
and mild shortness of breath; these prompted a chest X-ray, which was abnormal.
The radiograph showed a diffuse reticulonodular pattern worse in the upper lung
zones with some pleural thickening noted on the right. Breath sounds were clear,
heart exam unremarkable, and extremities without cyanosis or clubbing. The
hematocrit was 37.8. Other than a diagnosis of hypertension, there had been no
specific history of cardiovascular disease.

The patient's occupational history at that time consisted of 32 years of work
in an iron pipe foundry, with the last 28 spent in a high-dust environment as a
core maker--an individual who prepares silicate forms around which castings are
founded. He had worked without respiratory protection until the last few years,
and he had never smoked tobacco. Pulmonary function studies were consistent with
a mild restrictive pattern: forced vital capacity (FVC) = 2.72 L or 73% of
predicted; forced expiratory volume ([FEV.sub.1]) = 2.24 L or 75%;
[FEV.sub.1]/FVC = 82%; forced expiratory flow (FEF) 25-75 = 57% of predicted (14
March 1996). Based upon this history and the X-ray findings, a differential
diagnosis of silicosis, sarcoid, or tuberculosis was considered. Purified
protein derivative (PPD) skin testing was positive at 22 x 15 mm of induration.
The patient was treated with isoniazid, rifampin, and pyrazinamide pending
results of sputum stains and cultures for acid-fast bacilli (AFB). When these
studies were negative, he was changed to prophylactic treatment with 6 months of
isoniazid.

In late 1997, almost 2 years later, the patient experienced increased cough
and shortness of breath accompanied by rales on examination and progression of
chest radiograph findings. Films had been read on two separate occasions by two
separate chest-radiograph readers and found to be consistent with
pneumoconiosis. Despite a probable diagnosis of pneumoconiosis, objective
evidence of disease progression prompted an effort to secure a tissue diagnosis.
Via video-assisted thoracoscopy, therefore, wedge biopsies of the lung were
taken from the right middle and lower lobes. The initial pathology produced a
clinical diagnosis of silicosis that was later expanded to include asbestosis.
Although asbestosis is predominantly a lower lung disease radiographically, the
presence of asbestos bodies in regions of parenchymal fibrosis supports this
diagnosis pathologically as outlined elsewhere in this paper. A more recent
chest radiograph (early 2000) demonstrated a stable pattern of severe
interstitial lung disease, pleural and parenchymal scarring, and mild
hyperinflation (Figure 1). Spirometry and lung volumes (2 June 2000) are
consistent with mild restriction: FVC = 2.47 L or 67% of predicted; [FEV.sub.1]
= 1.85 L or 62%; [FEV.sub.1]/FVC = 75%; residual volume (RV) = 1.32 L or 78%;
total lung capacity (TLC) = 3.96 L or 74%; and RV/TLC = 33%. Diffusion capacity
was mildly reduced at 18.4 mL/mmHg/min or 67% of predicted.

[ILLUSTRATION OMITTED]

Detailed Pathologic Examination

Hematoxylin and eosin-stained tissue sections were screened via an A O Micro
Star Light microscope (American Optical Corporation, Buffalo, NY) at 100/400x
magnification. The open lung biopsy material submitted for tissue analysis via
digestion was collected in glutaraldehyde fixative that had been prefiltered
through 0.2 [micro]m polycarbonate filters. The tissue submitted for analytical
assessment was prepared in accordance with a procedure described elsewhere (1).
The digestion pool was made from approximately one-half of the eight pieces of
submitted tissue. The sample of material contained 1.18 g wet (0.143 g dry)
tissue. The procedure used for analysis by analytical transmission electron
microscopy is described elsewhere (2). The direct method of sampling enabled a
scan of a cleared mixed cellulose ester (Millipore Corporation, Bedford, MA)
filter (pore size 0.22 [micro]m) by light microscopy, to assess the presence of
particulates and ferruginous bodies.

We used a classification system applied in our earlier study of foundry
workers (3) to distinguish the various types of ferruginous-coated particles as
observed by light microscopy. A replica preparation was made of the surface
material collected on a polycarbonate filter (0.2 [micro]m pore size Nucleopore;
Nucleopore Corporation, Pleasanton, CA). The grids from this preparation were
scanned in a JEOL 100cx ATEM instrument (JEOL USA, Inc., Peabody, MA) at 16,000x
magnification for fibers. Additional scans were made at 10,000x to assess the
nonfibrous particulate burden. A 1,600x additional scan permitted greater area
assessment to detect ferruginous bodies. We performed core analysis on the
various types of coated structures.

We analyzed fibrous particulates as well as the core of the ferruginous bodies
by selected area diffraction and X-ray energy dispersive analysis (EDAX-NX-2
analyzer; EDAX, Inc., Mahwah, NJ). All fibers [is greater than or equal to] 0.5
[micro]m with an aspect ratio greater than five to one were evaluated in the
scans.

Results

Light Microscopy

Tissue sections. A review of the tissue section by light microscopy revealed
areas of parenchymal involvement characterized by appreciable numbers of
macrophages. Interstitial fibrosis occurred adjacent to the areas of greater
tissue involvement.

We observed small polarizable particulates within the macrophages. These
crystalline structures varied in shape. Occasionally we found in the presence of
the diffuse interstitial fibrosis one or more ferruginous bodies that were
morphologically consistent with asbestos bodies (Figure 2). This observation
supported a diagnosis of asbestosis based on pathologic criteria (4,5).
Orientation within the tissue sections occasionally permitted recognition of a
ferruginous coating deposited on a thin black filament (Type B) as shown in
Figure 3. A thick, black rod was also occasionally found as a core structure. An
example of this Type C ferruginous body is shown in Figure 4. We observed no
ferruginous bodies in the tissue sections that suggested formation on larger
plates or "flake-like" structures (Type D).

[ILLUSTRATION OMITTED]

Digested Material. A light microscopy assessment of a cleared wedge of mixed
cellulose ester filter revealed a heavy particulate burden consisting
predominantly of small black particles. We saw occasional larger aggregates of
the same density as the smaller structures. Many of the smaller particulates as
well as larger structures were birefringent in polarized light. There was a
mixture of ferruginous body (FB) types found on the slides (Table 1). There were
132 classical ferruginous bodies whose typical appearance (clear, elongated
fibrous core) suggested that these were formed on asbestos (asbestos bodies).
Tissue concentration was equivalent to 5,280 FB/g wet weight (ww) of tissue
(43,560 FB/g dry weight [dw]). The limit of detection was 40 FB/g ww (330 FB/g
dw).
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Applying the classification scheme used earlier (3) to distinguish types of
ferruginous bodies from foundry workers, we found that the digested material
contained seven Type B ferruginous bodies (a core consisting at the light
microscopy level of a thin black filament). The cores of these ferruginous
bodies were determined by analytical transmission electron microscopy to be
formed on an organic filament. There were 19 Type C ferruginous bodies (having a
core of thickened black rod), which were also determined to be of a carbon
composition. There was one ferruginous body found by light microscopy, formed on
a "flake-like" or plate material which had varying degrees of ferruginous
deposits along its periphery. This body, which was not elongated, could not be
confused with an asbestos body based upon its morphology. Electron Microscopy

The material collected on the polycarbonate filter for ATEM analysis
represented 0.04 g ww (0.00485 g dw) aliquot of the digestion pool. A high
magnification scan (16,000x) of 0.36 [mm.sup.2] revealed 98 fibers. These fibers
were analyzed by both X-ray dispersive analysis (XEDS) and selected area
diffraction. There were 24 uncoated amphibole asbestos fibers [23 anthophyllite
(Figure 5) and one tremolite] in the scanned area (Table 2). Figures 6 and 7
show the respective X-ray energy dispersive analysis spectrum and an amphibole
diffraction pattern of a typical anthophyllite fiber. The 24 asbestos fibers
were equivalent to 641,667 fibers/g ww (5,293,750 fibers/g dw). The limit of
detection at 16,000x was 26,736 fibers/g ww (220,573/g dw). Seventy-four other
nonasbestos fibers were found in the screen. These included 47 aluminum
silicates, some of which had iron and other ions as components, 8 titanium
fibers, 6 crystalline silica fibers, and 2 organic fibers. The remaining fibers
were of mixed magnesium silicates with combinations of other ions. The total
burden of nonasbestos fibers consisted of 1,978,472 fibers/g ww (16,322,386
fibers/g dw).

An additional lower magnification scan at 1,600x over 7.02 [mm.sup.2] yielded
six elongated ferruginous bodies. The respective core of each was comprised of
anthophyllite (Figure 8), tremolite, crystalline silica, one organic fiber
(Figure 9), a fiber rich in magnesium aluminum silicates (MgAlSi) and one
totally coated core (unidentifiable). There was one Type D ferruginous body
which we determined was formed on aluminum silicates (Figure 10). [ILLUSTRATIONS
OMITTED]

All of the nonasbestos fibers were shorter than 5 [micro]m. Sixty-nine percent
of the anthophyllite fibers were shorter than 5 [micro]m, whereas the average
length of the remaining 31% was 14 [micro]m (Table 3).
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A particulate analysis carried out at 10,000x revealed an overall moderate
burden. Crystalline silica comprised 8% of the particulate burden. The low
concentration of silica did not coincide with the pathologic and clinical
suspicion of silicosis. However, the tissue received for electron microscopy
analysis was not fully representative of involved lung zones originally
determined clinically to support this diagnosis. The highest percentage of
particulate was iron-rich particles (35%) and aluminum silicates (45%).
Discussion

A 53-year-old man was evaluated for suspected pneumoconiosis as suggested by
occupational history and reticulonodular pattern on chest radiograph with
pleural thickening. The individual had worked in a foundry/metal reclamation
facility for 32 years. By their nature, these facilities are dusty work
environments, which can create accumulation in the lung of mixed dust burdens
including silica, various silicates, ferrous material, as well as fiberglass
(3,2). The morphology of the inhaled particulates consists of both fibrous and
nonfibrous dust.

In a previous study, lavage material from five individuals who worked in
similar foundries revealed the presence of four morphologically distinct types
of ferruginous bodies as seen by light microscopy (3) and classified as Types
A,B,C, or D. These included typical-appearing ferruginous bodies (Type A),
formed predominantly on asbestos, as revealed by analytical electron microscopy.
Infrequently, the cores were fiberglass or thin transparent sheet silicates.

The second form of ferruginous body as defined by light microscopy had as its
core a thin black filament determined by electron microscopy to be composed of
amorphic organic material (Type B). The filament was sufficiently thin that its
detection would be in question at lower magnification scans by light microscopy.
Another form (Type C) appeared to be composed of the same material, but
contained a much thicker black core. These were easily distinguished by light
microscopy and subsequently confirmed by electron microscopy as organic.

The final form of ferruginous body (Type D) was not confused with the other
elongated forms of ferruginous bodies that occur on fibrous cores because the
material comprising the cores in these entities were plates or "flake-like"
structures, and often displayed a yellowish dark golden coloration. The striking
feature among these five patients, as well as in lung tissue from other foundry
workers submitted to our facility, is the abundance of ferruginous-coated
material within the lung. In light of the present patient's work history and his
pulmonary status, tissue samples were submitted for digestion and analysis by
light and electron microscopy.

This case has consistent findings as well as unique factors when compared with
observations from the previous study of foundry workers (3).

The lung tissue from the present case was found to contain "classical
ferruginous bodies" which by morphologic definition could be considered asbestos
bodies by light microscopy (5) and occurring at levels above that observed from
general populations (6-8). Similar to our previous observations (3), this
individual had nonasbestos cored ferruginous bodies, most of which, by light
microscopy, could easily be distinguished from asbestos bodies.

Analysis by ATEM identified the core material of ferruginous bodies to include
nonasbestos (organic material, crystalline silica, MgAlSi) and "noncommercial"
asbestos (anthophyllite, tremolite) fibers. The latter contrasts with the
findings of the previous study (3) where asbestos bodies were formed on amosite
cores--an amphibole considered a "commercial" asbestos.

Exposure to various dusts has long been recognized in foundry settings (9).
The rare occurrence of a nonelongated ferruginous body in this case differs from
our findings of their common occurrence in samples from workers from another
East Texas foundry (3).

Other distinctions between this case and our previous report exist in the
uncoated fiber burden. Uncoated chrysotile or amosite asbestos fibers were found
in lavage from four of the five previously studied workers.

The anthophyllite form of asbestos has been reported to be of no commercial
significance in the United States (10). To our knowledge, the use of
anthophyllite in the United States consists largely of two manufacturing
facilities in Delaware and a small facility in Minnesota. The anthophyllite was
brought to the facilities from Finland. In fact, Finland, through its mining
opportunities in a quarry at Paakkila, represented the world's commercial mining
output of this type of asbestos (11). No records have been found that indicate
that products manufactured with anthophyllite were ever used in the foundry
where the patient in this case worked.

Not surprisingly, limited data exist in the United States about cases where
elevated exposure to anthophyllite has occurred. The significant presence of
ferruginous bodies formed on anthophyllite in women has been linked to products
such as cosmetic talc, or anthophyllite-contaminated clay where this asbestos
was considered a component of the primary mineral used in the product
(6,7,12-15)

Churg and Warnock (15) have noted that from a medical viewpoint the
"noncommercial" types of asbestos such as anthophyllite are most likely to be
encountered as natural contaminants of other minerals. When such noncommercial
fibers are found in tissue from the general population, they are usually shorter
than 5 [micro]m (8,15). The population of anthophyllite fibers in this
individual is represented by considerable numbers of fibers longer than 5
[micro]m. The presence of longer fibers of anthophyllite is more consistent with
findings from individuals with a history of asbestos exposure in the workplace
where 67% of the anthophyllite was longer than 5 [micro]m (1). In the present
case, 23 of the 24 asbestos fibers were anthophyllite; the remaining uncoated
fiber was tremolite.

The limited data have shown that in the United States elevated exposures to
anthophyllite have occurred among talc workers (16) and in commercial talc
manufacturing (17). The presence of anthophyllite and tremolite in talc from the
Gouverneur Talc District of New York has been verified by several studies,
including a Bureau of Mines Report of Investigations in 1985 (18). A report by
the government of British Columbia has noted that talc was used in the United
States in 1996 in numerous products, including ceramics, paint, paper, plastics,
roofing, and cosmetics. Additional applications included insecticides, rubber,
refractories, and other products (19). It has also been reported that there is
direct use of talc in some foundry applications (20). While a material
containing talc could be suspect as a source of the anthophyllite in this case,
a specific product has not yet been identified.

In the present case, we found no uncoated fibers of the "commercial types" of
asbestos, in contrast to findings from previous studies involving foundry
workers (3). Key observations in this case included the levels of tissue burden
of anthophyllite as well as the qualitative composition of the fibers,
appreciably different from expected findings in the general population (8,15).
Further, the type of asbestos found was inconsistent with those described in
most published observations of workplace exposures reported in the United
States. It is reasonable, therefore, that this individual's exposure occurred
from a product that, by content, consisted mostly of a nonasbestos mineral in
which there was an appreciable component of anthophyllite.

Prognostically, this individual is at risk for progression of silicosis as
well as fibrosis due to asbestos. The presence of asbestosis also places him at
increased future risk of cancer. Adding to the complexity in this case is the
identification of a considerable burden of "noncommercial" asbestos with a
yet-to-be defined exposure source.

The instructive nature of this case centers around the concern with how many
other similar exposures may occur in which asbestos is not considered a
contributor to disease or risk of future disease. This omission may occur
because historical links of exposure to asbestos-containing products in the
workplace or environment are not immediately evident. This realization may have
significant implications for clinical prognostic reasons as well as medical and
legal concerns.